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https://www.readbyqxmd.com/read/28726535/mismatch-repair-deficient-metastatic-colon-cancer-and-urothelial-cancer-a-case-report-of-sequential-immune-checkpoint-therapy
#1
Pooja Ghatalia, Rajeswari Nagarathinam, Harry Cooper, Daniel M Geynisman, Wafik S El-Deiry
A major recent advance in cancer therapy involves the use of immune checkpoint therapy for tumors with mismatch repair deficiency, as they have a high tumor mutation load and neoantigen burden. Approximately 4% of advanced colorectal cancer harbors a mismatch repair deficiency. When mismatch repair deficiency exists in the germline, there is increased susceptibility to a variety of cancers including colorectal cancer, uterine cancer, urothelial carcinoma, and skin cancer. Herein we report the case of a 62-year-old man with mismatch repair deficient metastatic colorectal adenocarcinoma, urothelial carcinoma and a history of sebaceous carcinomas...
July 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28725428/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#2
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725427/progressive-hypoventilation-due-to-mixed-cd8-and-cd4-lymphocytic-polymyositis-following-tremelimumab-durvalumab-treatment
#3
Sooraj John, Scott J Antonia, Trevor A Rose, Robert P Seifert, Barbara A Centeno, Aaron S Wagner, Ben C Creelan
BACKGROUND: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur. CASE PRESENTATION: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725344/complete-response-of-mediastinal-clear-cell-sarcoma-to-pembrolizumab-with-radiotherapy
#4
Samuel Marcrom, Jennifer F De Los Santos, Robert M Conry
BACKGROUND: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28725048/cd300f-il-5-cross-talk-inhibits-adipose-tissue-eosinophil-homing-and-subsequent-il-4-production
#5
Perri Rozenberg, Hadar Reichman, Israel Zab-Bar, Michal Itan, Metsada Pasmanik-Chor, Carine Bouffi, Udi Qimron, Ido Bachelet, Patricia C Fulkerson, Marc E Rothenberg, Ariel Munitz
Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation of Il5 (Tg) /Cd300f (-/-) mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Consequently, Il5 (Tg) /Cd300f (-/-) mice had increased alternatively activated macrophage accumulation in the adipose tissue...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#6
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#7
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#8
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723666/increased-cflip-expression-in-thymic-epithelial-tumors-blocks-autophagy-via-nf-%C3%AE%C2%BAb-signalling
#9
Djeda Belharazem, Albert Grass, Cornelia Paul, Mario Vitacolonna, Berthold Schalke, Ralf J Rieker, Daniel Körner, Philipp Jungebluth, Katja Simon-Keller, Peter Hohenberger, Eric M Roessner, Karsten Wiebe, Thomas Gräter, Thomas Kyriss, German Ott, Peter Geserick, Martin Leverkus, Philipp Ströbel, Alexander Marx
The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown.Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723287/advanced-renal-cell-carcinoma-role-of-the-radiologist-in-the-era-of-precision-medicine
#10
Atul B Shinagare, Katherine M Krajewski, Marta Braschi-Amirfarzan, Nikhil H Ramaiya
For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC...
August 2017: Radiology
https://www.readbyqxmd.com/read/28722673/expression-and-clinical-association-of-programmed-cell-death-1-programmed-death-ligand-1-and-cd8-lymphocytes-in-primary-sarcomas-is-subtype-dependent
#11
Anke E M van Erp, Yvonne M H Versleijen-Jonkers, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Mark A J Gorris, Laura S van Dam, Thomas Mentzel, Marije E Weidema, C Dilara Savci-Heijink, Ingrid M E Desar, Hans H M Merks, Max M van Noesel, Janet Shipley, Winette T A van der Graaf, Uta E Flucke, Friederike A G Meyer-Wentrup
In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively)...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721906/immune-checkpoint-inhibition-in-cancers-that-affect-the-head-and-neck
#12
Janaki Parameswaran, Barbara Burtness
No abstract text is available yet for this article.
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#13
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28721019/inhibitors-of-the-pd-1-pd-l1-axis-for-the-treatment-of-head-and-neck-cancer-current-status-and-future-perspectives
#14
REVIEW
Xiongwen Ran, Kai Yang
Head and neck cancer (HNC) is a common malignant tumor, but traditional therapeutic methods have unsatisfactory curative effects and many complications occur. Hence, there is an urgent need to develop therapeutic methods that can elicit curative effects as well as low toxic and few side effects. With the development of cancer molecular biology and immunology, targeted therapy for immune checkpoints of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has shown enormous development prospects for HNC treatment...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#15
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28720430/oncogenic-pathways-that-affect-antitumor-immune-response-and-immune-checkpoint-blockade-therapy
#16
REVIEW
Xianda Zhao, Subbaya Subramanian
Mechanistic insights of cancer immunology have led to the development of immune checkpoint blockade therapy (ICBT), which has elicited a remarkable clinical response in some cancer patients. Increasing evidence suggests that activation of oncogenic pathways, such as RAS/RAF/MAPK and PI3K signaling, impairs the antitumor immune response. Such oncogenic signaling, in turn, activates many inhibitory factors, including expression of immune checkpoint genes-allowing active infiltration of immunosuppressive cells into the tumor environment and inducing resistance against T-cell killing...
July 15, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#17
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28719380/comparison-of-different-antibody-clones-for-immunohistochemistry-detection-of-programmed-cell-death-ligand-1-pd-l1-on-non-small-cell-lung-carcinoma
#18
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28719055/endocrine-toxicity-of-immune-checkpoint-inhibitors-essential-crosstalk-between-endocrinologists-and-oncologists
#19
REVIEW
Frédéric Illouz, Claire Briet, Lucie Cloix, Yannick Le Corre, Nathalie Baize, Thierry Urban, Ludovic Martin, Patrice Rodien
Two types of immune checkpoint inhibitors, both antibodies that target cytotoxic T-lymphocyte antigen-4 and those that target programmed cell death-protein 1, have been approved for use in melanoma, non-small-cell lung cancer, and renal cell carcinoma as first-line or second-line therapy. Their adverse events are primarily regarded as immune-related adverse events. We felt it was important to pinpoint and discuss certain preconceptions or misconceptions regarding thyroid dysfunction, hypophysitis, and diabetes induced by immune checkpoint inhibitors...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718428/ifn-signaling-and-icb-resistance-time-is-on-tumor-s-side
#20
Alejandro López-Soto, Segundo Gonzalez, Alicia R Folgueras
Activation of antitumor immunity upon immune checkpoint blockade (ICB) is one of the most promising strategies in cancer therapy. However, ICB resistance is frequently observed in cancer preclinical models and patients. A recent report in Cell reveals that sustained interferon (IFN) signaling confers tumor resistance to ICB by inducing the expression of an immunosuppressive multigenic program.
March 2017: Trends in Cancer
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